The emerging challenge in diabetes: the "metabolic memory".

Large randomized studies have established that early intensive glycemic control reduces the risk of diabetic complications, both micro and macrovascular. However, epidemiological and prospective data support a long-term influence of early metabolic control on clinical outcomes. This phenomenon has recently been defined as "metabolic memory." Potential mechanisms for propagating this "memory" may be the production of reactive species unrelated to the presence of hyperglycemia, depending on the previous production of AGEs which can maintain RAGE over-expression, on the level of glycation of mitochondrial proteins and on the amount of mtDNA produced, all conditions able to induce an altered gene expression which may be persistent even when glycemia is normalized. Clinically, the emergence of this "metabolic memory" suggests the need for a very early aggressive treatment aiming to "normalize" the metabolic control and the addition of agents which reduce cellular reactive species and glycation in addition to normalizing glucose levels in diabetic patients in order to minimize long-term diabetic complications.